van Wonderen Stefan F, Vermeulen Christie, Lagerberg Johan, Vlaar Alexander P J, Klei Thomas R L
Department of Intensive Care, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.
Department of Product and Process Development, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands.
Transfus Med Rev. 2025 Jul;39(3):150904. doi: 10.1016/j.tmrv.2025.150904. Epub 2025 May 23.
For decades, di(2-ethylhexyl) phthalate (DEHP) has been the primary plasticizer used to make polyvinyl chloride (PVC) blood bags flexible. DEHP leaches into the blood product, stabilizing red blood cell (RBC) membranes and preventing excessive hemolysis. Despite being classified as a substance of very high concern due to its potential endocrine-disrupting and carcinogenic effects, DEHP has continued to be used in red cell concentrate (RCC) storage bags, as alternatives have often led to reduced RCC quality during storage. However, under the European Medical Device Regulation the use of DEHP in medical devices is restricted to below 0.1% by weight per July 2030. As a result, the effect of several alternative plasticizers on RCC quality, such as di(2-ethylhexyl) terephthalate (DEHT), 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), and N-butyryl-n-hexyl citrate (BTHC), have recently been investigated in combination with different storage solutions. Although previous studies using these new combinations showed variable results, these alternatives remain the most promising options, with current data demonstrating reduced leaching and lower toxicity compared to DEHP. This review highlights key publications on the transition from DEHP-PVC blood bag systems for RCC storage, demonstrating that several non-DEHP alternatives are viable replacement options, particularly when combined with next-generation storage solutions. Future studies are required to assess the frequency of adverse events, the occurrence of handling issues such as leakage, and to evaluate practical performance and clinical efficacy through post-transfusion recovery and increment studies.
几十年来，邻苯二甲酸二（2-乙基己基）酯（DEHP）一直是用于使聚氯乙烯（PVC）血袋具有柔韧性的主要增塑剂。DEHP会渗入血液制品中，稳定红细胞（RBC）膜并防止过度溶血。尽管由于其潜在的内分泌干扰和致癌作用而被列为高度关注物质，但DEHP仍继续用于红细胞浓缩液（RCC）储存袋中，因为替代物常常会导致储存期间RCC质量下降。然而，根据欧洲医疗器械法规，到2030年7月，医疗器械中DEHP的使用限制在重量百分比低于0.1%。因此，最近研究了几种替代增塑剂，如对苯二甲酸二（2-乙基己基）酯（DEHT）、1,2-环己烷二羧酸二异壬酯（DINCH）和柠檬酸正丁酰正己酯（BTHC）与不同储存溶液组合对RCC质量的影响。尽管先前使用这些新组合的研究结果各不相同，但这些替代物仍然是最有前景的选择，目前的数据表明，与DEHP相比，它们的浸出量减少且毒性更低。这篇综述重点介绍了关于从用于RCC储存的DEHP-PVC血袋系统过渡的关键出版物，表明几种非DEHP替代物是可行的替代选择，特别是与下一代储存溶液结合使用时。未来需要进行研究，以评估不良事件的发生频率、诸如渗漏等处理问题的发生率，并通过输血后恢复和增量研究来评估实际性能和临床疗效。
